Bulletin of the American Physical Society
APS March Meeting 2012
Volume 57, Number 1
Monday–Friday, February 27–March 2 2012; Boston, Massachusetts
Session L42: Focus Session: Physics of Cancer II -- Physical Aspects |
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Sponsoring Units: DBIO Chair: Clare Yu, University of California, Irvine Room: 156C |
Tuesday, February 28, 2012 2:30PM - 3:06PM |
L42.00001: A Condensed Matter Physicist Looks at Cancer and the Tumor Microenvironment Invited Speaker: Clare Yu We will discuss what physics can bring to cancer biology, and give an example by taking a closer look at the tumor microenvironment. Cancer cells do not act alone. They get their cues from the their environment which consists of the extracellular matrix and the cells (fibroblasts) that form it. These cues can be both chemical and mechanical in nature. [Preview Abstract] |
Tuesday, February 28, 2012 3:06PM - 3:18PM |
L42.00002: Senescent cells in growing tumors Stefano Zapperi, Caterina A.M. La Porta, James P. Sethna Tumors are defined by their intense proliferation, but sometimes cancer cells turn senescent and stop replicating. In the stochastic cancer model in which all cells are tumorigenic, senescence is seen as the result of random mutatations, suggesting that it could represent a barrier to tumor growth. In the hierarchical cancer model a subset of the cells, the cancer stem cells, divide indefinitely while other cells eventually turn senescent. Here we formulate cancer growth in mathematical terms and obtain distinct predictions for the evolution of senescence in the two models. We perform experiments in human melanoma cells which confirm the predictions of the hierarchical model and show that senescence is a reversible process controlled by survivin. We conclude that enhancing senescence is unlikely to provide a useful therapeutic strategy to fight cancer, unless the cancer stem cells are specifically targeted. [Preview Abstract] |
Tuesday, February 28, 2012 3:18PM - 3:30PM |
L42.00003: Clustering of brain tumor cells: a first step for understanding tumor recurrence Evgeniy Khain, M.O. Nowicki, E.A. Chiocca, S.E. Lawler, C.M. Schneider-Mizell, L.M. Sander Glioblastoma tumors are highly invasive; therefore the overall prognosis of patients remains poor, despite major improvements in treatment techniques. Cancer cells detach from the inner tumor core and actively migrate away [1]; eventually these invasive cells might form clusters, which can develop to recurrent tumors. In vitro experiments in collagen gel [1] followed the clustering dynamics of different glioma cell lines. Based on the experimental data, we formulated a stochastic model for cell dynamics, which identified two mechanisms of clustering. First, there is a critical value of the strength of adhesion; above the threshold, large clusters grow from a homogeneous suspension of cells; below it, the system remains homogeneous, similarly to the ordinary phase separation. Second, when cells form a cluster, there is evidence that their proliferation rate increases. We confirmed the theoretical predictions in a separate cell migration experiment on a substrate and found that both mechanisms are crucial for cluster formation and growth [2]. In addition to their medical importance, these phenomena present exciting examples of pattern formation and collective cell behavior in intrinsically non-equilibrium systems [3]. \\[4pt] [1] A. M. Stein et al, Biophys. J., 92, 356 (2007). \\[0pt] [2] E. Khain et al, EPL 88, 28006 (2009). \\[0pt] [3] E. Khain et al, Phys. Rev. E. 83, 031920 (2011). [Preview Abstract] |
Tuesday, February 28, 2012 3:30PM - 3:42PM |
L42.00004: Targeting tumor acidity Yana K. Reshetnyak, Donald M. Engelman, Oleg A. Andreev One of the main features of solid tumors is extracellular acidity, which correlates with tumor aggressiveness and metastatic potential. We introduced novel approach in targeting of acidic tumors, and translocation of cell-impermeable cargo molecules across cellular membrane. Our approach is based on main principle of insertion and folding of a polypeptide in lipid bilayer of membrane. We have identified family of pH Low Insertion Peptides (pHLIPs), which are capable spontaneous insertion and folding in membrane at mild acidic conditions. The affinity of peptides of pHLIP family to membrane at low pH is several times higher than at neutral pH. The process of peptides folding occurs within milliseconds. The energy released in a result of folding (about 2 kcal/mol) could be used to move polar cargo across a membrane, which is a novel concept in drug delivery. pHLIP peptides could be considered as a pH-sensitive single peptide molecular transporters and conjugated with imaging probes for fluorescence, MR, PET and SPECT imaging, they represent a novel in vivo marker of acidity. The work is supported by NIH grants CA133890 and GM073857 to OAA, DME, YRK. [Preview Abstract] |
Tuesday, February 28, 2012 3:42PM - 3:54PM |
L42.00005: Stress Modulus of Cancer Cells Keith Bonin, Martin Guthold, Xinyi Guo, Justin Sigley Our main goal is to study the different physical and mechanical properties of cells as they advance through different stages of neoplastic transformation from normal to the metastatic state. Since recent reports indicate there is significant ambiguity about how these properties change for different cancer cells, we plan to measure these properties for a single line of cells, and to determine whether the changes vary for different cellular components: i.e. whether the change in physical properties is due to a change in the cytoskeleton, the cell membrane, the cytoplasm, or a combination of these elements. Here we expect to present data on the stress modulus of cancer cells at different stages: normal, mortal cancerous, immortal cancerous, and tumorigenic. The cells are Weinberg cell line Human Mammary Epithelial (HME) cells. Atomic force microscope (AFM) probes with different diameters are used to push on the cell membrane to measure the local, regional and global cell stress modulus. Preliminary results on normal HME cells suggests a stress modulus of 1.5 $\pm$ 0.8 kPa when pushing with 7 $\mu$m spherical probes. We anticipate reporting an improved value for the modulus as well as results for some of the Weinberg cancer cells. [Preview Abstract] |
Tuesday, February 28, 2012 3:54PM - 4:06PM |
L42.00006: Cancer-stroma evolutionary dynamics in stress-gradient microenvironment Amy Wu, Guillaume Lambert, Robert Austin, James Sturm, Zayar Khin, Ariosto Silva In order to study the evolution of drug resistance in cancer, it is important to mimic the tumor microenvironment, in which cells are exposed to not uniform concentrations but rather gradients of drugs, nutrients, and other factors Compared to traditional in-vitro methods, microfluidic structure enables better control of the temporal and spatial profile of gradients. Here we demonstrate a microfluidic Doxorubicin gradient environment with heterogeneous landscape, and culture multiple myeloma (8226-S, expressing RFP) and bone marrow stroma (HS-5, expressing GFP) cell lines together. The myeloma cells are not directly motile, but they are able to migrate via the adhesion to motile stroma cells. The indirect motility mechanism of the myeloma cells is crucial for the adaptation to stress environment. Finally, we will report the co-culture dynamics under the stress of doxorubicin gradients, observing for cellular migrations and growth [Preview Abstract] |
Tuesday, February 28, 2012 4:06PM - 4:18PM |
L42.00007: Dynamic density functional theory of solid tumor growth: Preliminary models John Lowengrub Cancer is a complex system whose dynamics and growth result from nonlinear processes coupled across wide ranges of spatio-temporal scales. The current mathematical modeling literature addresses issues at various scales but the development of theoretical methodologies capable of bridging gaps across scales needs further study. We present a new theoretical framework based on Dynamic Density Functional Theory (DDFT) extended, for the first time, to the dynamics of living tissues by accounting for cell density correlations, different cell types, phenotypes and cell birth/death processes, in order to provide a biophysically consistent description of processes across the scales. We present an application of this approach to tumor growth. [Preview Abstract] |
Tuesday, February 28, 2012 4:18PM - 4:30PM |
L42.00008: The physics of Eukaryotic cell crawling through elastic media Elnaz Alipour Baum-Snow, Charles Wolgemuth Understanding the motion of cells through deformable media, such as the extra-cellular matrix (ECM), is important for understanding many biological processes, such as cancer metastasis, wound healing, and organismal development. Crawling eukaryotic cells exert dipole-distributed traction stresses on the external environment. These stress distributions pull backwards at the front of the cell and forward at the rear of the cell. Recent experiments have shown the magnitude of the deformations induced in a collagen matrix by migrating cancer cells. We propose a model to understand cell movements through the ECM, by considering a dipole-crawler moving through an isotropic, linear elastic medium. This model captures the major features of the deformations that are induced by motile cancer cells in collagen. In addition, the model suggests that the deformations that are induced in the matrix can provide a mechanism by which distal cells can interact with one another through matrix-mediated interactions. We, therefore, study the forces, torques, and trajectories of two cells migrating through the ECM. Our analysis suggests a mechanism that may be relevant for the collective migration of cells during cancer metastasis and other processes where numerous cells move through the ECM. [Preview Abstract] |
Tuesday, February 28, 2012 4:30PM - 4:42PM |
L42.00009: Monte Carlo Simulations for Radiobiology Nicole Ackerman, Magdalena Bazalova, Kevin Chang, Edward Graves The relationship between tumor response and radiation is currently modeled as dose, quantified on the mm or cm scale through measurement or simulation. This does not take into account modern knowledge of cancer, including tissue heterogeneities and repair mechanisms. We perform Monte Carlo simulations utilizing Geant4 to model radiation treatment on a cellular scale. Biological measurements are correlated to simulated results, primarily the energy deposit in nuclear volumes. One application is modeling dose enhancement through the use of high-Z materials, such gold nanoparticles. The model matches in vitro data and predicts dose enhancement ratios for a variety of in vivo scenarios. This model shows promise for both treatment design and furthering our understanding of radiobiology. [Preview Abstract] |
Tuesday, February 28, 2012 4:42PM - 4:54PM |
L42.00010: A two-phase mixture model of avascular tumor growth Deniz Ozturk, M. Burcin Unlu, Sirin Yonucu, Ugur Cetiner Interactions with biological environment surrounding a growing tumor have major influence on tumor invasion. By recognizing that mechanical behavior of tumor cells could be described by biophysical laws, the research on physical oncology aims to investigate the inner workings of cancer invasion. In this study, we introduce a mathematical model of avascular tumor growth using the continuum theory of mixtures. Mechanical behavior of the tumor and physical interactions between the tumor and host tissue are represented by biophysically founded relationships. In this model, a solid tumor is embedded in inviscid interstitial fluid. The tumor has viscous mechanical properties. Interstitial fluid exhibits properties of flow through porous medium. Associated with the mixture saturation constraint, we introduce a Lagrange multiplier which represents hydrostatic pressure of the interstitial fluid. We solved the equations using Finite Element Method in two-dimensions. As a result, we have introduced a two-phase mixture model of avascular tumor growth that provided a flexible mathematical framework to include cells' response to mechanical aspects of the tumor microenvironment. The model could be extended to capture tumor-ECM interactions which would have profound influence on tumor invasion. [Preview Abstract] |
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